Striking a Nerve: Respect the Lowly Case Report

by John Gever John Gever Managing Editor, MedPage Today
August 12, 2014

It isn't often that a single patient's experience can drive a new treatment approach for a common illness, but that may be happening right now in Alzheimer's disease.

A report in JAMA Neurology describes a 40-year-old African-American man with an unusual constellation of symptoms: wacky blood lipids including total cholesterol levels approaching 800 mg/dL and numerous xanthomas on his hands, feet, ears, and buttocks. Statin and fibrate therapy had no effect on the lipids.

In the absence of an obvious clinical diagnosis, researchers led by Mary J. Malloy, MD, of the University of California San Francisco performed a comprehensive genetic analysis. They eventually determined that the man had two copies of a mutant APOE gene that left him without any apolipoprotein E.

The apoE protein is normally found throughout the central and ocular nervous systems and has been thought to be functionally critical. So Malloy and colleagues were surprised to find that the patient had no abnormalities in vision, brain MRI scans, cerebrospinal fluid composition, or clinical neurological exam findings.

Cardiovascular function was also largely normal for a man his age, with some signs of cardiac ischemia and mild hypertension.

The lack of visual and neurocognitive deficits "suggests either that functions of apoE in the brain and eye are not critical or that they can be fulfilled by a surrogate protein," Malloy and colleagues concluded.

Here's the broader significance: since the man has managed to do without the apoE protein for his entire life with only relatively minor abnormalities, it suggests that drug treatments seeking to knock it down won't be inherently toxic.

This has particular implications for Alzheimer's disease, for which the APOE4 gene variant (encoding a slightly misshapen apoE protein) is by far the biggest risk factor. It's been proposed that targeting this protein could prevent or delay onset of Alzheimer's disease in APOE4 carriers, but the counterargument has been that it would probably cause more neurological problems than it would solve.

Now, with this case report in hand, it's a good bet that drug companies will be taking a new look at anti-apoE treatments.

Striking a Nerve is a blog by John Gever for readers interested in neurology and psychiatry.

The work was supported by foundation grants and private gifts. Authors declared they had no relevant financial interests.

More in Neurology

MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals.

Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities.